Pulmonary inflammation and glucocorticoid sensitivity for the prediction of bronchopulmonary dysplasia (PRIDICT-BPD): a feasibility study

Rationale: Preterm infants (< 30 weeks of gestation) who develop bronchopulmonary dysplasia (BPD) are at high risk of cognitive impairments and cerebral palsy.
The adrenal cortex of preterm infants is immature, resulting in a cortisol level that is too low for the degree of illness. Novel data suggest that not only the production but also the action of cortisol is
impaired in this group. Both can result in insufficient damping of pulmonary inflammation, which is considered a key pathway in the development of BPD. Prophylactic treatment with
systemic corticosteroids is effective for the prevention of BPD, but has been associated with increased risk of adverse neurocognitive development. It is generally assumed that infants at
high risk of BPD may benefit from corticosteroids, whereas in low-risk infants the adverse effects of this treatment probably outweigh the beneficial effects. However, clinical prediction
models for BPD lack accuracy. We propose a novel strategy for the prediction of BPD that includes assessment of 1. adrenocortical output, 2. glucocorticoid bioactivity, 3. singlenucleotide
polymorphisms (SNPs) in corticosteroid-responsive genes expressed during lung development, and 4. pulmonary inflammation.

Objective: To test whether the assays described above are feasible to develop a prediction model for BPD in the future.

Study design: Prospective follow-up study during the initial hospital admission.

Study population: Fifty infants born <30 weeks of gestation.

Intervention (if applicable): N/A

Main study parameters/endpoints: Determinants are: [1] adrenocortical output and [2] glucocorticoid bioactivity measured in (cord) blood at the day of birth and at postnatal days 3,
7, 14 and 28; [3] single-nucleotide polymorphisms in corticosteroid-responsive genes expressed during lung development measured in cord blood or placental tissue; and, [4]
pulmonary inflammation, as assessed by volatile organic compounds (VOCs) in exhaled breath and interleukins in blood obtained at above time points. Outcomes are the rate and
severity of BPD, and the level and duration of respiratory support.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Improving outcomes in the growing population of extremely preterm
infants is one of the major challenges in neonatal care today. There are no burdens or risks associated with participation in this study. In addition to cord blood, blood (cumulative
amount: 2 ml over a 28 day period) will always be drawn at the same time as for routine clinical care, so that no additional vena puncture or heel stick procedures are required for this
study. Furthermore, the decision to start treatment with corticosteroids will remain at the discretion of the treating physician and will not be based on the assays being tested.

Prediction of the development of bronchopulmonary dysplasia in preterm infants including assessment of the adrenal gland function and pulmonary inflammation.

Postpartum, day 3, day 7, day 14 and day 28.

NA